TARGETED THERAPIES THEIR CUTANEOUS...

TARGETED THERAPIES &

THEIR CUTANEOUS TOXICITIES

Consensus guidelines for skin toxicity

EGFR inhibitors

Monoclonal antibodies - Cetuximab (Erbitux®) - Panitumumab (Vectibix®) Oral tyrosine kinase inhibitors - Erlotinib (Tarceva®) - Gefitinib (Iressa®) - Lapatinib (Tyverb®) - Afatinib (Giotrif®)

EGFR INHIBITORS

General preventive measures

- sun protection

- measures for skin hydratation

- loose-fitting shoeware and cotton socks

3

EGFR INHIBITORS

General preventive measures

- sun protection:

• Avoid intense sun (2 hours before and after noon (12 till 4pm)

• Use physical protection of the skin with suitable clothing

• Apply a strong sunscreen (SPF 30-50) on sun-exposed areas

• Limit the total dose of UV on the skin

4

EGFR INHIBITORS

General preventive measures

- measures for skin hydratation • Reduce washing frequency

• Avoid hot water

• Adapted soaps: fatty soap, shower/bath oil

• Use emolliens / nutrient cream

e.g. ureum 1% in cetomacrogol cream or in cold cream

5

EGFR inhibitors

Papulopustular eruption

EGFR INHIBITORS: papulopustular eruption

• > face, upper trunk (V shape)

• majority of patients

• more pronounced in monoclonal antibodies than in TKIs

• negative impact on the quality of life

• within 2 weeks from start of therapy • peaks after 4-6 weeks with gradual decrease afterwards

Epidemiology

7

EGFR INHIBITORS: papulopustular eruption

- prescription for early* start of treatment skin toxicity

Preventive measures

* Early is defined as starting on day 1 of treatment or starting at the earliest signs of skin toxicity 8

EGFR INHIBITORS: papulopustular eruption

GRADE 1 (mild) Mild eruption No symptoms No impact on ADL*

Clinical presentation and management

* ADL: activities of daily living 9

EGFR INHIBITORS: papulopustular eruption

TREATMENT Topical - Metronidazole cream 1/d Rozex® cream or emulsion, Rosaced®, Nidazea® Systemic - Tetracyclin antibiotics minocyclin 1x100mg/d lymecycline 1x300mg/d or - postpone to grade 2

Clinical presentation and management

GRADE 1 (mild)

10

EGFR INHIBITORS: papulopustular eruption

Clinical presentation and management

GRADE 2 (moderate) Moderate eruption Some symptoms mainly itch Minor impact on ADL*

* May affect instrumental ADL, no effect on self-care 11

EGFR INHIBITORS: papulopustular eruption

TREATMENT Topical - Metronidazole cream 1/d Rozex® cream or emulsion, Rosaced®, Nidazea® - Corticoid: mild or moderate potent Systemic - Tetracyclin antibiotics minocyclin 1 to 2x100mg/d lymecycline 1 to 2 x300mg/d Symptomatic antihistamin (older antihistamines stronger itch reducing effect but more sedation)

Clinical presentation and management

GRADE 2 (moderate) Re-evaluate after 2 weeks – if not better refer to dermatologist

12

EGFR INHIBITORS: papulopustular eruption

Clinical presentation and management

GRADE 3 (severe) Severe eruption Severe symptoms Major impact on ADL*

* Affects ADL both instrumental and self-care 13

EGFR INHIBITORS: papulopustular eruption

Clinical presentation and management

GRADE 3 (severe)

TREATMENT Refer to dermatologist Topical - Corticoid: moderate potent Systemic - Tetracyclin antibiotics minocyclin 2x100mg/d; lymecycline 2x300mg/d or -Isotretinoin 20-30mg/d

Symptomatic antihistamin (older antihistamines stronger itch reducing effect but more sedation) If not reacting on therapy consider dose delay

14

EGFR inhibitors

Xerosis / Eczema

EGFR INHIBITORS: xerosis / eczema

• may affect whole skin

• affects quality of life: itch

• starts from 4 to 8 weeks after treatment initiation

Epidemiology

16

EGFR INHIBITORS: xerosis / eczema

Clinical presentation

17

EGFR INHIBITORS: Xerosis / Eczema

Management xerosis

- measures for skin hydratation • Reduce washing frequency

• Avoid hot water

• Adapted soaps: fatty soap, shower/bath oil

• Use emolliens / nutrient cream

e.g. ureum 1% in cetomacrogol cream or in cold cream

18

EGFR INHIBITORS: Xerosis / Eczema

Use corticoid cream on areas of eczema:

Face: mild to moderate corticoid

Body: moderate to potent corticoid

Management Eczema

19

EGFR inhibitors

Paronychia

EGFR INHIBITORS: paronychia

• starts from 8 weeks after treatment initiation

• mainly involving big toes

Epidemiology

21

EGFR INHIBITORS: paronychia

Clinical presentation

22

EGFR INHIBITORS: Paronychia

- Cotton socks

- Adapted shoeware: loose-fitting

Preventive measures

23

EGFR INHIBITORS: Paronychia

- Antiseptic baths e.g. chlorhexidin, Isobetadin

- Local: ultrapotent corticoid

- Systemic: NSAID (short time), tetracyclines

Management

24

EGFR INHIBITORS: granuloma pyogenicum

Clinical presentation

25

EGFR INHIBITORS: Granuloma pyogenicum

- local silver nitrate

- curettage

Management

26